Synaptic Connectivity and Cortical Maturation Are Promoted by the ω-3 Fatty Acid Docosahexaenoic Acid

Abstract

Brain development is likely impacted by micronutrients. This is supported by the effects of the ω-3 fatty acid docosahexaenoic acid (DHA) during early neuronal differentiation, when it increases neurite growth. Aiming to delineate DHA roles in postnatal stages, we selected the visual cortex due to its stereotypic maturation. Immunohistochemistry showed that young mice that received dietary DHA from birth exhibited more abundant presynaptic and postsynaptic specializations. DHA also increased density and size of synapses in a dose-dependent manner in cultured neurons. In addition, dendritic arbors of neurons treated with DHA were more complex. In agreement with improved connectivity, DHA enhanced physiological parameters of network maturation in vitro, including bursting strength and oscillatory behavior. Aiming to analyze functional maturation of the cortex, we performed in vivo electrophysiological recordings from awake mice to measure responses to patterned visual inputs. Dietary DHA robustly promoted the developmental increase in visual acuity, without altering light sensitivity. The visual acuity of DHA-supplemented animals continued to improve even after their cortex had matured and DHA abolished the acuity plateau. Our findings show that the ω-3 fatty acid DHA promotes synaptic connectivity and cortical processing. These results provide evidence that micronutrients can support the maturation of neuronal networks.

Docosahexaenoic Acid and Lactoferrin Effects on the Brain and Placenta in a Rabbit Model of Intrauterine Growth Restriction 

“…These results are in line with previous data showing positive effects of Omega 3 fatty acids on dendritic arborization and new spine formation in the hippocampus during normal ageing 45,46 and on neurite length and branching in hippocampal embryonic neuronal cell cultures 47,48 . Interestingly, previous literature has demonstrated the link between enhanced neuronal dendritic growth in the motor cortex with motor functional improvements 49 .…”

Retinoid X Receptor α Regulates DHA-Dependent Spinogenesis and Functional Synapse Formation In Vivo

“…Unesterified DHA Regulates Synapse/Spine Density In Vivo through RXRA Long-term DHA deprivation (in weeks or months) in vivo has been shown to impair synapse function and cognition-related performance, while long-term DHA supplementation improved both parameters (Carbone et al, 2020;de la Presa Owens and Innis, 1999;Igarashi et al, 2011;Lafourcade et al, 2011;Nguyen et al, 2014;Ramakrishnan et al, 2009). However, the mechanism by which DHA regulates synapse function and/or cognition-related performance remains largely unknown.…”

“…However, the mechanism by which DHA regulates synapse function and/or cognition-related performance remains largely unknown. In vitro administration of unesterified DHA promoted synapse development on the timescale of hours to days (Cao et al, 2009;Carbone et al, 2020;Fujita et al, 2001;Mazzocchi-Jones, 2015). Why does it take so long?…”

“…It can be released from the membrane by phospholipases in a rapid Article ll OPEN ACCESS and dynamic process to participate in signal transduction in an unbounded (unesterified) state (Bazinet et al, 2006;Green et al, 2008;Purdon et al, 2002;Strokin et al, 2004). Previous studies have shown that DHA regulates excitatory synaptic transmission and synapse density in primary neuronal cultures (Cao et al, 2009;Carbone et al, 2020).…”

Pharmacological Neuroprotection of the Preterm Brain: Current Evidence and Perspectives

“…85 Since it accumulates in the brain mainly during the last trimester of pregnancy, 86 preterm birth is associated with early deficits in cortical DHA. 85 Animal studies have shown that dietary supplementation from birth with DHA alone or in mixture with eicosapentaenoic acid promotes synaptic connectivity and cortical processing, 87 and also protects the neonatal brain against hypoxic/ischemic injury. 88 Supplementation during pregnancy was also shown to protect against lipopolysaccharide (LPS)-induced white matter injury in the neonatal rat brain.…”